Download What and Where Information in the Caudate Tail Guides Saccades

The Journal of Neuroscience, August 8, 2012 • 32(32):11005–11016 • 11005
Behavioral/Systems/Cognitive
What and Where Information in the Caudate Tail Guides
Saccades to Visual Objects
Shinya Yamamoto,1,2 Ilya E. Monosov,1 Masaharu Yasuda,1 and Okihide Hikosaka1
1Laboratory of Sensorimotor Research, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892, and 2System Neuroscience, Human
Technology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba 305-8568, Japan
Weunderstandtheworldbymakingsaccadiceyemovementstovariousobjects.However,itisunclearhowasaccadecanbeaimedataparticular
object,becausetwokindsofvisualinformation,whattheobjectisandwhereitis,areprocessedseparatelyinthedorsalandventralvisualcortical
pathways. Here, we provide evidence suggesting that a basal ganglia circuit through the tail of the monkey caudate nucleus (CDt) guides such
object-directed saccades. First, many CDt neurons responded to visual objects depending on where and what the objects were. Second, electrical
stimulation in the CDt induced saccades whose directions matched the preferred directions of neurons at the stimulation site. Third, many CDt
neurons increased their activity before saccades directed to the preferred objects and directions of the neurons in a free-viewing condition. Our
results suggest that CDt neurons receive both “what” and “where” information and guide saccades to visual objects.
Introduction
In the visual association cortices, the processing of spatial
(“where”) information and object (“what”) information is
roughly segregated into the dorsal and ventral cortical visual
pathways (Mishkin et al., 1983; Goodale and Milner, 1992). This
hypothetical scheme poses a problem, however, when we plan to
make a motor action aiming at a particular object, say, by making
a saccadic eye movement. If a group of neurons in the ventral visual
pathway detect the object but encode little information on its position, how can they contribute to the saccade aiming at the position of
the object? One possibility is that the segregation of information
processing is not strict: object-selective neurons in the inferotemporal cortex may carry position information (Op De Beeck and Vogels,
2000; DiCarlo and Maunsell, 2003; Sereno and Lehky, 2011),
position-encoding neurons in the parietal or frontal cortex may
carry object information (Sereno and Maunsell, 1998; Murata et al.,
2000; Janssen et al., 2008; Peng et al., 2008), or the position and
object information may converge in the prefrontal cortical areas
(Rao et al., 1997; Rainer et al., 1998). It is unclear, however, whether
such convergent information is accurate enough to enable motor
actions aiming at particular objects.
One alternative mechanism underlying such “object-directed
actions” may be the neural circuits through the basal ganglia.
Received Feb. 20, 2012; revised June 2, 2012; accepted June 3, 2012.
Author contributions: S.Y., I.E.M., M.Y., and O.H. designed research; S.Y., I.E.M., and O.H. performed research; S.Y.
and O.H. analyzed data; S.Y., I.E.M., M.Y., and O.H. wrote the paper.
This work was supported by the intramural research program at the National Eye Institute. We thank E. S.
Bromberg-Martin, S. Hong, H. Kim, and Y. Tachibana for valuable discussions, and A. Hays, J. W. McClurkin, B. Nagy,
A. M. Nichols, D. Parker, T. W. Ruffner, M. K. Smith, G. Tansey, N. Phipps, C. Zhu, F. Ye, and D. Leopold for technical
assistance.
This article is freely available online through the J Neurosci Open Choice option.
Correspondence should be addressed to Shinya Yamamoto, Human Technology Research Institute, National
Institute of Advanced Industrial Science and Technology (AIST), 1-1-1, Umezono, Tsukuba 305-8568, Japan. E-mail:
[email protected].
DOI:10.1523/JNEUROSCI.0828-12.2012
Copyright © 2012 the authors 0270-6474/12/3211005-12$15.00/0
Studies using behaving monkeys have shown that the basal ganglia nuclei contain neurons that respond to visual stimuli in a
position-selective manner (Hikosaka et al., 2000) and may control motor actions by sending the position information to the
superior colliculus (Hikosaka and Wurtz, 1983b; Karabelas and
Moschovakis, 1985; Liu and Basso, 2008). The position information may be derived from the dorsal cortical visual pathway,
which heavily projects to the anterior part of the striatum, particularly the head and body of the caudate nucleus (Selemon and
Goldman-Rakic, 1985; Stanton et al., 1988; Shook et al., 1991;
Parthasarathy et al., 1992).
On the other hand, visual object information is transmitted predominantly to the tail of the caudate nucleus (hereafter referred to as
CDt). Highly developed in the primate (including humans and macaque monkeys), the CDt is a long caudal extension of the caudate
nucleus, lying along the temporal lobe (see Fig. 1A,B). Consistent
with this anatomical position, the CDt receives inputs mainly from
the temporal cortex, particularly cortical areas in the ventral visual
pathway (Yeterian and Van Hoesen, 1978; Van Hoesen et al., 1981;
Saint-Cyr et al., 1990; Webster et al., 1995; Middleton and Strick,
1996). Neurons in the CDt respond to visual stimuli in an objectselective manner (Caan et al., 1984; Brown et al., 1995). Furthermore, the CDt projects to the dorsolateral part of the substantia nigra
pars reticulata (SNr) (Saint-Cyr et al., 1990), which contains many
neurons projecting to the superior colliculus (SC) (Beckstead et al.,
1981). However, it is unclear whether CDt neurons encode position
information.
We found in behaving monkeys that CDt neurons encoded
not only what but also where information of visual objects, weak
electrical stimulation in the CDt induced saccades, and CDt neurons became active before saccades to particular positions and
particular objects.
Materials and Methods
We used two male rhesus monkeys (Macaca mulatta), Z and T. After each
monkey was sedated by general anesthesia, we implanted a head holder,
Yamamoto et al. • What and Where Visual Information in Caudate Tail
11006 • J. Neurosci., August 8, 2012 • 32(32):11005–11016
a chamber for unit recording, and eye coils. All animal care and experimental procedures were approved by the National Eye Institute Animal
Care and Use Committee and complied with the Public Health Service
Policy on the humane care and use of laboratory animals.
Behavioral tasks
Table 1. Object and position selectivity of visual responses in the caudate tail
Position selectivity
Yes
Object selectivity
Yes
No
All
No
All
76 (77%) (Z, 61; T, 15)
4 (4%) (Z, 2; T, 2)
80 (81%)
Behavioral tasks were controlled by a custom real-time experimentation
17 (17%) (Z, 13; T, 4)
2 (2%) (Z, 2; T, 0)
19 (19%)
data acquisition system (REX, Laboratory of Sensorimotor Research,
93 (94%)
6 (6%)
99 (100%)
National Eye Institute–National Institutes of
Health, Bethesda, MD) (Hays et al., 1982). Two
monkeys (Z and T) participated in the experiA
B
ments. The monkeys sat in a primate chair and
faced a front screen on which visual stimuli
were presented.
Fractals used as visual objects. We created visual stimuli using fractal geometry (Miyashita
et al., 1991). One fractal was composed of four
point-symmetrical polygons, which were overlaid around a common center such that smaller
polygons were positioned more front. The parameters that determined each polygon (size,
edges, color, etc.) were chosen randomly. Its
1 cm
1 cm
size was ⬃8 ⫻ 8°. We used a fixed set of eight
fractals (hereafter called “standard set of fracTRN
C
D
tals”) to examine all CDt neurons recorded. In
addition to this standard set of fractals, we used
many other sets of fractals. This allowed us to
LGN
st
STS
examine the responses of CDt neurons to fractals with different familiarity, particularly
novel fractals (which the monkey had never
CDt
seen before).
lv
Object-directed saccade task. The purpose of
this task was to examine the object and position
selectivity of CDt neurons. The monkey made a
saccade to a fractal object to obtain a fixed
amount of liquid reward (see Fig. 2 A). The tarHip
get object was chosen from a standard set of
eight fractals (see Fig. 2C, top) and was pre5 mm
1 mm
sented at one of five positions (see Fig. 2 B;
right, left, up, and down with the eccentricity of
15°, and the center). The task started with the Figure 1. AnatomyoftheCDt.A,AnMRimageincludingthecaudatetail.Theimageplaneistiltedlaterallyby25°inwhichmostofthe
presentation of a central spot of light [fixation electrode tracks to the CDt are included. The CDt is indicated by arrows. Below the CDt is the lateral ventricle (thin black portion) and the
point (FP)] on which the monkey had to fixate. hippocampus. B, MRI-reconstructed image of the caudate nucleus (red). The borders of the caudate at multiple planes parallel to the
After 700 ms, a fractal target (TG) was pre- electrode tracks are superimposed, together with the borders of the cerebrum, cerebellum, and brainstem. The anterior commissure is
sented, but the monkey was required to keep indicated by a green dot. The anterior part of the caudate includes the nucleus accumbens. C, D, Histological section of the recording site in
fixating on the fixation point. After an FP–TG the CDt. An electrolytic lesion made after recording of a single CDt neuron is found in the dorsolateral part of the CDt. Note that the CDt is
overlap period (600 ms for monkey Z; 450 ms surrounded by the posterior part of the putamen (Put), lateral geniculate nucleus (LGN), thalamic reticular nucleus (TRN), stria terminalis
for monkey T), the FP disappeared as a GO (st), lateral ventricle (lv), hippocampus (Hip), and fundus of the superior temporal sulcus (STS).
signal to make a saccade to the TG. When TG
was presented at the center, the monkey was
was determined by presenting the fractals at different positions before
not required to make any saccade. The criteria of fixation were ⫾4° for FP
recording or using the object-directed saccade task. In addition to the
and ⫾7° for TG. Therefore, when the TG was presented on the FP, the
standard set of eight fractals, we used novel object set to compare the
window of the criterion became large. The monkey received a liquid
visual response to novel and familiar objects.
reward after holding its gaze on the TG for 600 ms. The trial was aborted
Free-viewing condition. The purpose of this task was to examine the
if the monkey broke fixation. After the aborted trial, the same target was
activity of CDt neurons related to gaze orienting behavior in the presence
presented on the next trial. The target was chosen pseudorandomly such
of multiple visual objects. On every trial, four fractals were presented
that, within a subblock of 40 trials, the 8 fractals and the 5 positions were
simultaneously at four radially symmetrical positions (i.e., positions
randomized. For each neuron, at least 2 blocks (80 trials) were tested
shown in Fig. 12 A, or tilted by 45°) with the eccentricity of 15°. On each
(range, 2–11 blocks; median, 6 blocks).
odd-numbered trial, four fractals were chosen randomly from a set of
Passive-viewing task. The purpose of this task was to examine the object
eight fractal objects. On the following even-numbered trial, the remainselectivity of the visual responses of CDt neurons. Fractal objects were
ing four fractals were presented. Each fractal presentation lasted for 3000
presented while the monkey was fixating on the central FP. On each trial,
ms, which was followed by a 500 –700 ms blank period before the next
two to six fractals were chosen pseudorandomly from the standard set of
fractal presentation. During or between fractal presentations, no reward
eight fractals and were presented in sequence at the preferred position of
was delivered and the monkey was not required to do anything. Nonethe recorded neuron. Each fractal was presented for 400 ms, followed by
theless, the monkey looked at the fractals by making saccades frequently
a 500 –700 ms blank period. The presentation of the fractals started 600 –
from one fractal to another. The frequency of the saccades during the
800 ms after the monkey started fixating on the FP. A liquid reward was
fractal presentation was 2.0 ⫾ 0.7 times per second (mean ⫾ SD), which
given 500 –700 ms after the presentation of the last fractal, but it was not
ranged from 0 to 4.3. The amplitude of the saccades was 11.7 ⫾ 7.4°
associated with particular objects. The preferred position of the neuron
(mean ⫾ SD), which ranged from 0.1 to 46.1.
Yamamoto et al. • What and Where Visual Information in Caudate Tail
A
J. Neurosci., August 8, 2012 • 32(32):11005–11016 • 11007
B
Saccade
Up
Eye position
Fixation point
FP
Left
Target (fractal)
Center
Right
TG
Reward
700 ms 600 ms 600 ms
Fixation Target Hold on
target
Obj A
C
Right
Up
Obj C
Obj D
Obj E
Obj F
Obj G
Obj H
50
0
Spike rate (Hz)
Down
Obj B
Down
Left
Center
0
400
Time (ms)
Figure 2. Object and position coding of a CDt neuron. A, B, The object-directed saccade task. While the monkey was fixating on a central spot of light (FP), one of eight fractal objects (TG) (C, top)
was presented at one of five positions (B). The choice of the target object and position was based on a pseudorandom schedule. The monkey was allowed to make a saccade to the object only after
the fixation point disappeared, after which a liquid reward was delivered to the monkey. No saccade was required when the object appeared at the center. C, Responses of a neuron recorded in the
left CDt to the appearance of the fractal objects, shown separately for different objects (columns) and different positions (rows). This neuron showed a high selectivity to both object and position
information. The spike activity of the CDt neuron is shown by raster displays and spike density functions (SDFs) (␴: 10 ms). The time 0 indicates the onset of the fractal object. For this and other CDt
neurons, we used the same set of fractal objects (standard set) (Figs. 2–5) in addition to some other sets of objects.
To maintain the monkey’s arousal level, we included rewarded trials. After
every one to four fractal presentations, a small white dot appeared at one of
the other four positions 2 s later, and, if the monkey made saccade to and
fixated on it for 3 s, a liquid reward was given to the monkey.
Electrophysiology
Based on a stereotaxic atlas (Saleem and Logothetis, 2007), a rectangular
(28 mm anterior–posterior ⫻ 26 mm medial–lateral) or a circular (19mm-diameter) recording chamber was placed over the parietal cortex,
tilted laterally by 25°, and aimed at the tail of the CDt. MR images (4.7 T;
Bruker) were then obtained along the direction of the recording chamber, which was visualized with gadolinium that filled grid holes and
inside the chamber.
Single-neuron recordings and electrical stimulations were performed using tungsten electrodes (FHC; diameter, 0.25 mm; 1–3 M⍀; Alpha-Omega;
diameter, 0.39 mm; 1–3 M⍀). The recording (or stimulation) site was de-
termined using a grid system, which allowed electrode penetrations at every
1 mm. Based on the MR images and preceding recording data, we chose a
grid hole to hold the stainless-steel guide tube, through which the electrode
was inserted and was advanced by an oil-driven micromanipulator (MO97A; Narishige). Based on the grid hole position and the reading of the
electrode depth, we estimated the 3D position of the electrode.
The electrical signal from the electrode was amplified with a bandpass
filter (200 Hz to 10 kHz; BAK) and collected at 1 kHz via custom-made
window discriminator (MEX). Single neurons were isolated on-line using custom voltage–time window discrimination software (MEX, Laboratory of Sensorimotor Research, National Eye Institute–National
Institutes of Health, Bethesda, MD).
To find visually responsive CDt neurons, we let the monkey continue
to perform the passive-viewing task or the object-directed saccade task.
Since CDt neurons fired spikes only occasionally, we could find and
Yamamoto et al. • What and Where Visual Information in Caudate Tail
11008 • J. Neurosci., August 8, 2012 • 32(32):11005–11016
Down
50
0
Right
Spike rate (Hz)
Obj A
Up
Obj B
Obj C
Obj D
Obj E
Obj F
Obj G
Obj H
Left
Center
0
600
Time (ms)
Figure 3.
Responses of a neuron recorded in the left CDt. This neuron showed a higher selectivity to object information than to position information. The format is the same as in Figure 2.
Obj A
Obj C
Obj D
Obj E
Obj F
Obj G
Obj H
100
50
0
Right
Up
Spike rate (Hz)
Down
Obj B
Left
Center
0
600
Time (ms)
Figure 4.
Responses of a neuron recorded in the left CDt. This neuron showed a higher selectivity to position information than to object information. The format is the same as in Figure 2.
examine only those neurons that responded to these visual-saccade tasks.
It is thus likely that other nonvisual-saccadic neurons, if present, remained undetected or uncharacterized.
Electrical stimulation
To examine whether CDt neurons could induce saccades, we first identified the CDt by recording single neuronal activity responsive to fractals,
and then stimulated the CDt and surrounding areas using the same elec-
trode as a monopolar stimulating electrode. We used a train of biphasic
negative–positive pulses with 200 ␮s per phase duration (400 Hz; 300
ms) for the stimulation. The amplitude of the electrical currents was
20 – 60 ␮A. The stimulation experiment was done while the monkey was
in a free-viewing condition (fractal presentation time, 2000 ms; blank
period, 1000 ms). The liquid reward was given to the monkey after one to three
presentations of fractals, regardless of the monkey’s behavior. Within a subblock
Yamamoto et al. • What and Where Visual Information in Caudate Tail
Obj A
Obj B
J. Neurosci., August 8, 2012 • 32(32):11005–11016 • 11009
Obj C
Obj D
Obj E
Obj F
Obj G
Obj H
Monkey Z
20
0
Neuron #2
50
0
Neuron #3
Neuron #4
Neuron #5
Spike rate (Hz)
Neuron #1
Neuron #6
Neuron #7
50
0
50
0
20
0
100
0
50
0
Average of all
46 neurons
20
0
Monkey T
Average of all
16 neurons
50
0
-500 0 500
Time (ms)
Figure 5. Object selectivity of CDt neurons. The responses of seven CDt neurons to the standard set of fractal objects during the passive-viewing task (see Materials and Methods). While the
monkey was fixating on a central spot, two to six objects chosen pseudorandomly from the standard set were presented in sequence at the preferred position of the neuron (presentation time, 400
ms; interpresentation time, 500 –700 ms). The time 0 indicate the time when the object appeared. Bottom, The average responses of all CDt neurons from monkey Z (n ⫽ 46) and monkey T (n ⫽
16), shown separately for the objects (10 ms ␴ for SDFs). The standard set of objects was different between the two monkeys. Note that the preferred object, response pattern, and latency were
different among neurons, but the averaged responses to the objects were similar to each other.
of four trials, two trials were chosen randomly for electrical stimulation, one for
stimulation during the fractal presentation period and the other for stimulation
during the blank period. An electrical stimulation was applied at a random timing during the chosen period. These procedures were used to minimize the variation of the monkey’s arousal, cognitive, and emotional states.
Data analysis
Object and position selectivity of the visual responses of CDt neurons. For each
neuron that responded to fractal objects, we examined whether its response was
object and/or position selective. For this purpose, we conducted a two-way
ANOVA (5 positions ⫻ 8 objects) for neuronal activities during the objectdirected saccade task. The number of spikes during the FP–TG overlap period
(while the fractal object was present and while the monkey was fixating the
central fixation point) was used as a dependent variable (Table 1).
Object selectivity. The two-way ANOVA does not indicate which objects are preferred and how strongly they are preferred. To answer this
question, we performed a receiver operating characteristic (ROC) analysis comparing the response of the neuron to one object with its responses to the other objects. The responses for the best position of the
neuron were used for this analysis. Since we used the same standard set of
eight fractal objects for 86 neurons (65 neurons in monkey Z and 21
neurons in monkey T), the analysis yielded, for each neuron, eight values
corresponding to the area under the ROC curve. The vector of these
values is color-mapped for each neuron (see Fig. 6, vertical column).
To quantify how object selective each neuron was, we defined a selectivity
index (SI). The SI was calculated for each neuron using the averaged responses to
the most and least preferred objects among the eight objects: SI ⫽ (max ⫺
min)/(max ⫹ min) (Sereno and Maunsell, 1998; Sereno and Lehky, 2011).
In addition to the object selectivity for individual neurons, we asked
whether CDt neurons, as a population, responded to the standard objects
differentially. To answer this question, we conducted a Friedman’s test for
the data of the passive-viewing task (8 objects ⫻ 46 neurons).
Position selectivity. To examine the preferred positions of CDt neurons, we used two methods: one based on the object-directed saccade task
and the other based on the passive-viewing task.
Using the object-directed saccade task, we calculated the “center of
gravity” of visual responses based on the number of spikes during the
FP–TG overlap period using the following equation:
冘
冘
xជ p ⫻ fp
xជ COG ⫽
positions
positions
fp
,
Yamamoto et al. • What and Where Visual Information in Caudate Tail
11010 • J. Neurosci., August 8, 2012 • 32(32):11005–11016
Monkey Z
Monkey T
A
1
Up
ROC
Obj A
Obj B
Obj C
Obj D
Obj E
Obj F
Obj G
Obj H
Ipsi
Contra
0
Neuron
A
B 30
1
Novel
Number of neurons
SI for novel objects
20
0.5
10
0.5
1
Familiar
20
0
0.5
SI for familiar objects
D
60
60
Spike rate (Hz)
Response to novel objects (Hz)
1
Selectivity index (SI)
C
40
20
Novel
20
0
0
20
40
60
Response to familiar objects (Hz)
Monkey T
1
0
Figure 8. Position selectivity of CDt neurons. A, Preferred positions of all CDt neurons. For
each neuron, the center of gravity was computed based on the visual responses to the five
positions (Fig. 2 B) (see Materials and Methods) and is indicated by a dot. The neurons were
classified into two types depending on whether their visual responses at the center of gaze were
larger (red) or smaller (blue) than the average of the responses to the other four locations. Note
that the preferred positions are largely localized in the contralateral hemifield. B, The responses
of the CDt neurons to five positions were normalized and are color-coded across neurons (horizontal axis) for the two monkeys. The normalized responses were obtained using ROC areas,
which were calculated by comparing the magnitude of the response to each of the five positions
with the responses to the other four positions. The data in A and B were obtained using the
object-directed saccade task.
40
Familiar
0
Monkey Z
Contra
Up
Center
Down
Ipsi
0
30
0
0
5 deg
Neuron
10
0
B
Down
ROC
Figure 6. Distributed representation of objects among CDt neurons. The responses of CDt
neurons from monkey Z (n ⫽ 65) and monkey T (n ⫽ 21) to the standard set of eight objects
(A–H) are color-coded across neurons (horizontal axis). For each neuron (vertical column), we
normalized its responses to the eight objects (red, strong; blue, weak). For the normalization,
we calculated nonparametric ROC areas by comparing the magnitude of the response to each of
the eight objects with the responses to the other seven objects. The data were obtained using
the object-directed saccade task. Note that each object was most preferred by some of CDt
neurons.
0
500
Time (ms)
Figure 7. Object selectivity for novel and familiar stimuli of CDt neurons. A, SIs for novel and
familiar objects are plotted for individual CDt neurons. For each neuron, its responses were
examined separately for familiar objects (i.e., the standard set of 8 stimuli) and for novel objects
(a set of 8 newly created fractal objects). The data were obtained from 80 neurons using 2
familiar sets (1 for each monkey) and 80 novel sets of fractal objects. B, Distributions of SIs for
novel objects (top) and familiar objects (bottom). C, Response magnitudes for novel and familiar objects are plotted for individual CDt neurons. D, The average responses for novel and
familiar objects of the 80 CDt neurons.
where xជ COG, fp, and xជ p denote the center of gravity, the averaged firing rate
for each position, and the vector representation of each position [(15,0),
(0,15), (⫺15,0), (0,⫺15), (0,0) for the right, up, left, down, and center,
respectively] (see Fig. 8 A). We used the most preferred object of the
neuron for this calculation. This method does not take eccentricity into
account but indicates whether the neuron preferred peripheral positions
or central positions. We also performed an ROC analysis comparing the
response of the neuron to one position with its response to the other four
positions (see Fig. 8 B).
Using the passive-viewing task, we determined the preferred position
by presenting a preferred object at different positions while changing
both direction and eccentricity. The results provide a rough profile of the
receptive field of the neuron.
Saccades induced by electrical stimulation of the CDt. Since the monkey
made saccades spontaneously while the electrical stimulation was applied
occasionally, we needed to differentiate between the spontaneous saccades and the stimulation-induced saccades. To this end, we compared
the saccades that occurred during the electrical stimulation and the saccades that occurred during an equivalent behavioral state but with no
electrical stimulation.
For each electrical stimulation, we detected the saccade that occurred
first after the electrical stimulation started (but within 500 ms) as a candidate of a stimulation-induced saccade. The distribution of the vectors
of the first saccades (see Fig. 10 A) was smoothed with a two-dimensional
Gaussian kernel (␴ ⫽ 5°). We then defined a “movement field” as an area
whose values were ⬎60% of the peak value (after subtracting the background value).
Free-viewing condition. We hypothesized that the object-selective responses of CDt neurons can induce saccades to particular objects when
the monkey explore the visual environment regardless of reward outcome. To test the hypothesis, we analyzed the activity of CDt neurons in
the free-viewing condition in relation to such spontaneous saccades.
Among all saccades that occurred in the free-viewing condition, we concentrated on (1) the saccades directed to the most preferred object of the
neuron (among the eight objects) and (2) the saccades directed to the
least preferred object. We determined the most and least preferred objects using the passive-viewing task. Each group of saccades was further
divided into two groups: (1) saccades directed to the most preferred
direction of the neuron and (2) saccades directed to the least preferred
direction. We defined the most preferred direction to be within ⫾90° of
Yamamoto et al. • What and Where Visual Information in Caudate Tail
J. Neurosci., August 8, 2012 • 32(32):11005–11016 • 11011
the direction of the center of the receptive field
and the least preferred direction to be within
⫾90° of the opposite to the center or the receptive field. We then analyzed CDt activity separately for the four groups: most preferred and
least preferred (object by position) (see Figs.
12, 13). To analyze the population data, we
performed a three-way ANOVA (2 objects ⫻ 2
directions ⫻ 66 neurons) for the period of 200
ms before the saccade.
A
5 mm
Histology
B
AC -6
AC -7
AC -8
AC -9
AC -10
AC -11
AC -12
AC -13
5 deg
Figure 9. Variation of position selectivity (B) along the anterior–posterior axis of the CDt (A). In B, the preferred positions are
shown at each anterior–posterior location indicated in the MR image in A. Data were obtained from one monkey (monkey Z). The
anterior–posterior location was measured from the position of the AC. For example, “AC ⫺6” indicates “6 mm posterior from the
AC.” The preferred positions were computed as the centers of gravities for individual neurons. The MR image was aligned with
the electrode tracks (as in Fig. 1 A); the rectangular object at top is the recording chamber and reference grid (both filled with
gadolinium to allow MRI visualization).
In the later part of the experiments in monkey
T, we made electrolytic microlesions at the recording and stimulation sites (12 ␮A; 30 s). We
chose several sites for the microlesions along
the anterior–posterior axis of the CDt. For each
site, we made two to three microlesions with
different patterns of intervals, one of them usually inside the CDt. The animal was then deeply
anesthetized with pentobarbital sodium and
perfused with 4% paraformaldehyde. Frozen
sections were cut every 50 ␮m in the coronal
plane. The sections were stained with cresyl violet (see Fig. 1C,D).
C
B
30
0
-30
-30
0
30
Horizontal eye position (deg)
30
0
-30
0
500
Time (ms)
D
4
Saccade rate (/s)
Vertical eye position (deg)
A
Vertical eye position (deg)
Results
TRN
LGN
2
st
CDt
STS
Hip
lv
0
-200
0
200
Time (ms)
400
1 mm
Figure 10. Saccades induced by electrical stimulation of the CDt. A, B, Saccades during stimulation (40 ␮A) at a point in
the CDt, which is indicated by a pink arrow in D. A, The trajectories of the first saccades within 500 ms after electrical
stimulation started. The endpoints of the saccades are shown by red dots, and a movement field (see Materials and
Methods) is indicated by a yellow area. B, Superimposed vertical eye positions aligned on the electrical stimulation (gray
rectangle). The onsets of all saccades are indicated by a raster of short red lines. In A and B, the eye positions (expressed in
degrees) have been adjusted to zero at the beginning of the stimulation. C, The change in the probability of saccades into
the movement field relative to stimulation onset (black histogram). The saccades from multiple locations in the CDt (n ⫽
12) are included (Fig. 11). A gray line indicates the change in the probability of saccade into the movement field relative to
pseudostimulation onset (i.e., time at which electrical stimulation would have occurred but did not). The data in A–C were
obtained using the currents of 40 ␮A. D, Localization of the stimulation effects. In this coronal plane, electrical stimulation
was delivered along three adjacent electrode tracks. The vector (direction and amplitude) to the peak of the movement
field is shown by a yellow arrow whose starting point indicates the stimulation site. The crosses indicate the sites from
which no saccades were induced with the currents of 20 ␮A.
Encoding of what and where
information in the CDt
We recorded spike activity of single neurons in a wide area in the CDt in two monkeys while they viewed and made saccades
to fractal objects. We confirmed that the
locations of our neuronal recordings were
confined to the CDt in three ways. First,
we physiologically identified nearby structures, particularly the lateral geniculate
nucleus (Malpeli and Baker, 1975) (Fig.
1C,D), to guide the position of the recording electrode. Second, we observed neuronal spike shapes and firing patterns
typically observed within the primate
caudate nucleus (Hikosaka et al., 1989).
Third, we obtained definitive evidence of
our recording location by the histological
examination of electrolytic microlesions,
which were made at the end of the recording experiments (Fig. 1 D).
We found that many neurons in the
CDt responded to fractal objects, although it was unclear how prevalent such
object-responsive neurons were in the
CDt (see Materials and Methods). To examine the object and position selectivity
of CDt neurons, we used an objectdirected saccade task (Fig. 2 A). The target
object was chosen from a standard set of
eight fractals (Fig. 2C, top). On each trial,
one of the eight fractal objects was presented at one of five positions (Fig. 2 B),
and the monkey made a saccade to it to
obtain a fixed amount of reward (water or
juice).
A majority of the object-responsive
CDt neurons responded to the fractal ob-
11012 • J. Neurosci., August 8, 2012 • 32(32):11005–11016
Yamamoto et al. • What and Where Visual Information in Caudate Tail
jects in an object-selective and positionselective manner. Spike activity of an
A
example neuron recorded in the left CDt
is shown in Figure 2C. This neuron rarely
fired spikes spontaneously and thus was
considered to be a medium-spiny projection neuron (Plenz and Kitai, 1998). It responded with a brief excitation to some
objects (e.g., Obj F), particularly when
they were presented in the rightward direction (which was contralateral to the recording site) (Fig. 2C). Other examples
15 deg
1 mm
are shown in Figures 3 and 4.
A two-way ANOVA (object by position) revealed that, among 99 CDt
B
neurons that responded to fractal presentation, 76 neurons (77%; including neurons in Figs. 2C, 3, 4) showed significant
main effects of both object and position
( p ⬍ 0.05), 97 neurons (98%) showed
main significant effects of either object or
position ( p ⬍ 0.05), and 63 neurons
5 mm
(67%) showed significant effect of the inC
teraction of object and position ( p ⬍ 0.05;
AC -8
-9
-10
-11
-12
-13
-14
-16
Table 1). Thus, the CDt encodes both
what and where information about visual
objects.
The object selectivity varied across
CDt neurons (Fig. 5). Different neurons
15 deg
preferred different objects, and even the
responses of one neuron had different Figure 11. Variation of stimulation-induced saccades along the anterior–posterior axis of the CDt. A, The vector to the peak of
time courses across the objects (Fig. 5, the movement field is plotted at each stimulation site. The crosses indicate the sites from which no saccades were induced. The gray
compare neurons 1, 7). Overall, the aver- bar indicates the extent of the CDt estimated based on electrophysiological recording, six of which were confirmed histologically.
aged response across all neurons exam- B, The stimulation sites from which saccades were induced are plotted on a parasagittal MR image (white dots). C, The preferred
ined was similar across the objects (Fig. 5, positions of the visual responses of CDt neurons at the anterior–posterior locations that correspond to the data in A. The preferred
bottom) ( p ⫽ 0.66 for monkey Z and p ⫽ positions are shown for individual neurons (red dots) and their average (black dots). The anterior–posterior positions are measured
0.77 for monkey T, Friedman’s test). Con- from the anterior commissure (AC). Data were obtained from one monkey (monkey T).
versely, each object was most preferred by
tions. The horizontal coordinate of the center of gravity was
a fraction of CDt neurons (Fig. 6, indicated by red) and least
significantly deviated to contralateral side (mean ⫾ SD, 2.73 ⫾
preferred by a different fraction of CDt neurons (Fig. 6, blue).
3.04; p ⫽ 2.6 ⫻ 10 ⫺14, t test), but the vertical coordinate was not
These results suggest that, on average, the population of CDt
significantly deviated (mean ⫾ SD, ⫺0.02 ⫾ 4.65; p ⫽ 0.97, t
represented all of the eight objects comparably well.
test).
Note that both monkeys had seen the eight objects many times
In Figure 8 A, we divided CDt neurons into two groups by
during training and recording sessions. To test whether the object
comparing their responses to objects at the center with the other
preference of CDt neurons was acquired through experience, we
four positions in the object-directed saccade task: neurons that
created novel fractal objects and used them as additional visual
responded to the central position more strongly than to the avstimuli in the same task. We found that their responses to the
erage of four peripheral positions (red dots) and neurons that
novel objects were object selective similarly to the familiar objects
responded to the central position less strongly than to the average
(Fig. 7 A, B). There was no significant difference in the mean SI
of four peripheral positions (blue dots).
between novel objects (mean, 0.69) and familiar objects (mean,
We found that the representation of space is organized within
0.67) ( p ⫽ 0.31, paired t test). These results suggest that the
the CDt. In Figure 9B, the centers of gravity of CDt neurons (as
object-selective responses of CDt neurons do not require experishown in Fig. 8 A) are shown separately for different anterior–
ence. Note, however, that the magnitude of response was overall
posterior levels of recording, which are indicated on an MRI
stronger for novel stimuli than for familiar stimuli ( p ⫽ 2.8 ⫻
image (Fig. 9A). For example, the center of gravity was mostly
10 ⫺3, paired t test) (Fig. 7C,D).
upward at the position of AC ⫺12 [12 mm posterior from the
The position selectivity also varied across CDt neurons, but
anterior commissure (AC)], contralateral at AC ⫺9, and downtheir preferred directions were largely confined to the hemifield
ward at AC ⫺7. However, the same directions appear represented
contralateral to the recording sites (Fig. 8). To describe the spatial
more than once along the anterior–posterior axis, and therefore
properties of CDt neurons, we computed the center of gravity,
the spatial organization in the CDt is not a simple topographic
which is a directional vector based on the response magnitudes
map as seen in the primary visual cortex or the superior collicufor the five positions (Fig. 2 B) (see Materials and Methods). The
lus. Nonetheless, the CDt is different from other brain regions
data points close to the center correspond to neurons that responded to the center more strongly than the peripheral posiwith sharp object selectivity, such as the anterior inferotemporal
Yamamoto et al. • What and Where Visual Information in Caudate Tail
Eye position (deg)
10
0
-10
Horizontal
0
-10
-20
Vertical
-100
0
100
Time (ms)
Preferred
direction
Non-preferred
direction
Spike rate (Hz)
C
10
Spike rate (Hz)
Electrical stimulation in the CDt induces saccades
The output of the caudate nucleus, including that of the CDt, is
directed exclusively to other basal ganglia structures, specifically
the substantia nigra and the globus pallidus (Hikosaka et al.,
2000). In particular, the efferent connection of the CDt to the
dorsal part of the SNr (Saint-Cyr et al., 1990) suggests that the
CDt can modulate the initiation of saccadic eye movements, because this part of the SNr projects to the SC (Beckstead et al.,
1981) and has been demonstrated to play a role in the control of
saccadic eye movements (Hikosaka and Wurtz, 1983b).
We found indeed that electrical stimulation of the CDt induced saccades (Fig. 10). We stimulated the CDt (20 – 60 ␮A) at
random intervals while the monkey was free viewing fractal objects (see Materials and Methods). We first determined that the
electrode was within the CDt by recording from several neurons
showing object- and position-selective spike activity, which was
later confirmed histologically (Fig. 1 D). At this stimulation site,
the probability of saccades increased during the electrical stimulation (Fig. 10 B) and the saccades were largely directed upward
(Fig. 10 A). Based on the distribution of saccade endpoints, we
defined a movement field at this CDt site (Fig. 10 A, yellow area).
The probability of saccades to the movement field was elevated
just after the electrical stimulation started, peaked at ⬃100 ms,
and then gradually decreased to the baseline until the end of
electrical stimulation (Fig. 10C, black histogram). When there
was no electrical stimulation, there was no increase in the probability of saccades to the movement field (Fig. 10C, gray line).
These results indicate that the saccades to the movement field
were caused or facilitated by electrical stimulation of the CDt.
Hereafter, we call them stimulation-induced saccades.
We stimulated different sites in and around the CDt and
found similar results (Fig. 10 D). Other sites near the CDt were
mostly ineffective, even when they were ⬍1 mm medial, lateral,
or ventral to the CDt (Fig. 10 D). We occasionally found effective
patchy regions outside the CDt (Fig. 10 D, the right track), which
could be due to activation of a bundle of axons afferent to the CDt
or efferent from the CDt.
The stimulation-induced saccades varied depending on the
anterior–posterior position of the CDt (Fig. 11 A). At the site 12
mm posterior to the anterior commissure (AC ⫺12), the directions of stimulation-induced saccades were upward (as shown in
Fig. 10). Moving anteriorly from AC ⫺12, the saccade direction
rotated clockwise to rightward (i.e., contralateral) and slightly
downward. The directions of stimulation-induced saccades
roughly correlate with the preferred positions of visual responses
of CDt neurons recorded at the stimulation sites (Fig. 11C) (see
Materials and Methods). These data suggest that the visual object
information in the CDt could be transformed into saccadic motor information in a spatially heterogeneous manner.
Moving posteriorly from AC ⫺12, the amplitude, rather than
direction, changed from large (AC ⫺13) to small (AC ⫺16). In
these posterior regions, the effective sites covered 1–2 mm above
the CDt in addition to the CDt itself, but the stimulation-induced
saccades tended to be larger from the sites in the CDt. Unlike the
anterior regions, the directions of the stimulation-induced saccades were different from the preferred positions of the CDt neurons (mostly right-downward; Fig. 11C).
B
A
10
5
0
5
0
-1000
-500
0
500
1000
-1000
-500
0
Time (ms)
500
1000
Time (ms)
D
Spike rate (Hz)
cortex, which display no clear spatial organization (Tanaka,
1996). Thus, the CDt seems uniquely suited for controlling motor behavior aiming at visual objects.
J. Neurosci., August 8, 2012 • 32(32):11005–11016 • 11013
100
50
0
-500
0
500
Time (ms)
1000
-500
0
500
1000
Time (ms)
Figure 12. Comparison between presaccadic activation in the free-viewing condition and
visual responses in the passive-viewing task in a CDt neuron. A, Simultaneously presented
fractal objects which the monkey was allowed to look at freely with no reward outcome, while
activity of one CDt neuron was being recorded. The white line indicates the trajectory of a
saccade directed to the right, which is also shown in B as changes in horizontal (top) and vertical
(bottom) eye positions. At bottom of B are shown spikes of the CDt neuron that occurred before
the saccade. C, The spike activity of the neuron aligned on saccades directed to the most preferred (left column) and the least preferred (right column) objects of the neuron, separately for
the preferred (top row) and the nonpreferred (bottom row) directions of the neuron (20 ms ␴
for SDFs). The time 0 indicates the time when the saccades started. Since the preferred direction
was horizontally rightward (contralateral), the saccades collected in the free-viewing condition
were grouped into “preferred” if their directions were within ⫾90° from the horizontal rightward and “nonpreferred” if their directions were within ⫾90° from the horizontal leftward. D,
The responses of the neuron to the most preferred object (left) and least preferred object (right)
in the passive-viewing task. The objects were presented at the preferred position of the neuron,
rightward. The time 0 indicates the time when the object appeared. The object disappeared at
400 ms.
Neuronal activity during free viewing
These data suggest that the CDt has a mechanism to influence
saccades but do not indicate that the CDt actually transmits signals before the initiation of saccades. Since the visual responses of
CDt neurons are object selective, the CDt neurons may contribute to the initiation of saccades only when the saccades are directed to the preferred objects of the neuron. To test this
hypothesis, we first determined the object and position preference of a CDt neuron using the passive-viewing task and the
Yamamoto et al. • What and Where Visual Information in Caudate Tail
11014 • J. Neurosci., August 8, 2012 • 32(32):11005–11016
Spike rate (Hz)
Spike rate (Hz)
Spike rate (Hz)
Spike rate (Hz)
responses were rank-ordered to determine
B
A
Preferred
Non-preferred
the most- and least-preferred objects (Fig.
object
object
12D) (see Materials and Methods). We then
recorded the activity of the neuron while the
10
10
monkey was freely looking at multiple obPreferred
5
jects (Fig. 12A–C). In the free-viewing condirection
dition, four fractal objects were chosen
0
randomly from a set of eight objects and
were presented simultaneously for 3 s (Fig.
5
10
12A). Even though no reward was given after the object presentation, the monkey typNon-preferred
5
direction
ically looked at these objects by making
saccades between objects several times in the
0
0
-1000 -500 0
500 1000 -1000 -500 0
500 1000
3 s period. An example saccade is shown in
-400
-200
0
Time (ms)
Time (ms)
Time (ms)
Figure 12, A and B (top), together with spike
C
Red: preferred object
activity of a CDt neuron (Fig. 12B, bottom).
Blue: non-preferred object
50
50
In Figure 12C, the activity of the CDt
Solid line: preferred direction
Dotted line: non-preferred direction
neuron is aligned on saccades that were
directed to the most preferred (left) and
the least preferred (right) objects of the
0
0
neuron. In each case, the activity of the
-500
0
500
1000 -500
0
500
1000
neuron was further divided into two
Time (ms)
Time (ms)
groups based on the directions of the saccades: the preferred (top) and the nonpre- Figure 13. Presaccadic activation of CDt neurons in a free-viewing condition: population data. The same format as in Figure 12,
ferred (bottom) directions of the neuron. C and D, but spike activity has been averaged across 66 CDt neurons. For this analysis, we excluded saccades that were preceded by
The neuron became active before saccades another saccade within 500 ms to minimize the effect of such preceding saccades. A, The averaged spike activity aligned on
only when they were directed to the pre- saccades directed to the most preferred (left column) and the least preferred (right column) objects of the neurons (10 ms ␴ for
ferred object and when the saccades oc- SDFs), separately for the preferred (top row) and the nonpreferred (bottom row) directions of the neurons. A three-way ANOVA
curred in the preferred direction (Fig. (object by direction by neuron) showed significant main effects of object, position, and neuron ( p ⬍ 0.05). Spike activity during a
200 ms period before the saccade (dark colored region) was used for the analysis. B, The averaged presaccadic activity superim12C, top left).
A similar object direction selectivity posed for the four conditions. C, The responses of the same 66 neurons to the most preferred objects (left) and least preferred
objects (right) in the passive-viewing task.
was commonly observed in CDt neurons,
as indicated by the population data (coltomical data (Yeterian and Van Hoesen, 1978). A majority of
lected from 66 CDt neurons) (Fig. 13). To see the time course of
neurons in the caudate nucleus are medium spiny neurons that
the presaccadic activity more clearly, we collected saccades that
have hyperpolarized resting potentials (Plenz and Kitai, 1998)
were not preceded by another saccade within 500 ms. As shown in
and therefore are unlikely to be activated by these inputs individFigure 13B, the average spike activity grew larger when saccades
ually. Consistent with this view, many of the CDt neurons we
were directed to the preferred object in the preferred direction
recorded rarely fired spikes spontaneously (Figs. 2C, 3, 4). Accompared with the other saccades in ⬍200 ms before the saccade
cording
to this scheme, the object-selective inputs from the anteonset (Fig. 13B). These data are consistent with the hypothesis
rior
ITC
could activate CDt neurons only when there are
that individual CDt neurons contributes to the initiation of sacadditional
inputs from the posterior ITC that carry largely concades directed to specific objects located in specific positions.
tralateral positional information (Boussaoud et al., 1991). This
may be what we observed in many CDt neurons.
Discussion
Regardless of the underlying mechanism, the object- and
Our experiments have shown that many neurons in the monkey
position-selective
information provides CDt neurons with a cerCDt respond to fractal pictures in object- and position-selective
tain
advantage
in
controlling
motor behavior aiming at particular
manners. The object selectivity is expected from anatomical studobjects. However, its role is probably not exclusive. For example,
ies showing that the cortical areas in the ventral visual pathway
the dorsal cortical visual pathway, which is considered to transproject to the CDt (Yeterian and Van Hoesen, 1978; Van Hoesen
mit mainly position-selective information, contains neurons that
et al., 1981; Saint-Cyr et al., 1990; Webster et al., 1995) and is
respond to visual objects selectively (Sereno and Maunsell, 1998;
consistent with two previous single-unit recording studies (Caan
Murata et al., 2000; Janssen et al., 2008; Peng et al., 2008). The
et al., 1984; Brown et al., 1995). However, the position selectivity
prefrontal cortex, which is thought to play an executive role in
in CDt neurons is unexpected, since position selectivity tends to
goal-directed motor behavior, contains neurons that encode
become weaker along the ventral visual pathway (Boussaoud et
both position and object information (Rao et al., 1997; Rainer et
al., 1991). One explanation would be that object-selective neual., 1998). The position– object information in the parietal–fronrons in the inferotemporal cortex (ITC) may carry position intal cortical areas may converge on to the frontal eye field (Peng et
formation (Op De Beeck and Vogels, 2000; DiCarlo and
al., 2008) or area LIP (Sereno and Amador, 2006) from which
Maunsell, 2003; Lehky et al., 2008; Sereno and Lehky, 2011). In
saccadic commands may be issued. What then could distinguish
addition to receiving inputs from the anterior ITC, individual
between the basal ganglia mechanism and the parietal–frontal
CDt neurons may receive inputs from multiple cortical areas
cortical mechanism? A difference may be found in the effect of
along the ventral visual pathway, including the areas in its earlier
familiarity. The object selectivity in the prefrontal cortical neustages, such as the central and posterior ITCs, and area V4, which
rons increases with experience (Rainer and Miller, 2000). In conretain some positional information. This is supported by ana-
Yamamoto et al. • What and Where Visual Information in Caudate Tail
trast, CDt neurons discriminate novel fractal objects equally as
well as familiar fractal objects (Fig. 7 A, B). Therefore, the CDt
seems to have a built-in mechanism to precisely discriminate
large sets of visual objects and their locations. However, the
proposed difference between the cortical and basal ganglia
mechanisms needs to be tested experimentally under the same
behavioral context.
CDt neurons are also capable of inducing a motor behavior,
specifically saccadic eye movements. This conclusion was obtained from two sets of data: (1) saccades were induced by electrical stimulation of the CDt, and (2) CDt neurons increase their
activity before spontaneous saccades to objects. Each set of data
provides deeper insights into the mechanisms and functions of
the CDt.
The stimulation-induced saccades were likely due to activation of CDt neurons, because the threshold for evoking saccades
was quite low, comparable with the threshold for the frontal eye
field (FEF) (Bruce et al., 1985) or SC (Robinson, 1972), and was
lower than the threshold for area LIP (Shibutani et al., 1984).
More importantly, the sites effective for evoking saccades are
largely confined in and adjacent to the CDt (Figs. 10, 11). Such
scrutiny led to another intriguing finding: spatial organization
within the CDt. By slightly changing the site of electrical stimulation, the vector (direction and amplitude) of the stimulationinduced saccade changed significantly (Fig. 11). Furthermore,
the varying saccade vector roughly corresponded to the visual
receptive fields of nearby CDt neurons. This suggests that the
contralateral visual hemifield is represented in the CDt in a spatially heterogeneous manner and that the spatial organization
may be useful for inducing saccades to specific locations.
The CDt stimulation induced saccades at variable timings
(Fig. 10 B, C), similarly to the stimulation of the caudate head in
the cat (Kitama et al., 1991). This is in sharp contrast with the
stimulation of the FEF (Robinson and Fuchs, 1969) or SC (Robinson, 1972), which evoked saccades with nearly constant latencies. It is as if the CDt stimulation opened a gate for saccades to be
evoked based on signals from structures outside the CDt. In fact,
the caudate nucleus, at least its anterior portion (head or body), is
known to exert a facilitatory effect on the SC by removing the
tonic inhibition from the SNr to the SC (Hikosaka et al., 2000). It
is feasible that the CDt has the same mechanism. While the SC is
disinhibited by the CDt stimulation, saccadic motor neurons in
the SC would be activated if there are other excitatory inputs, say,
from the FEF. Note that, if the CDt works as a gate for saccade
initiation, the gating should be both position selective and object
selective. In fact, the SNr–SC connection carries positionselective signals: SNr neurons have restricted visual receptive
fields (Hikosaka and Wurtz, 1983a) and project to the part of the
SC with similar response fields (Hikosaka and Wurtz, 1983b).
Furthermore, SNr neurons respond to fractals in an objectselective manner, although the selectivity is weaker than that of
CDt neurons (our unpublished observation). Each CDt neuron,
assuming that it has an inhibitory connection to the SNr, would
contribute to the opening of the gate, but only when the preferred
object of the neuron is present (what) in the preferred position of
the neuron (where). In this scenario, other excitatory inputs may
not need to carry precise what–where information but should
determine the precise timing of the saccade. Neurons in the FEF
or LIP, which may provide such excitatory inputs, do carry what
information (Sereno and Maunsell, 1998; Peng et al., 2008).
However, according to a comparison using the same object selectivity index (see Materials and Methods), the object selectivity of
CDt neurons (mean SI, 0.67 for familiar objects; 0.69 for novel
J. Neurosci., August 8, 2012 • 32(32):11005–11016 • 11015
objects) was considerably higher than the object selectivity of FEF
neurons (mean SI, 0.25) or LIP neurons (mean SI, 0.35). We thus
speculate that, for making saccades to visual objects, the CDt–
SNr–SC pathway may determine what, whereas the FEF/LIP–SC
pathway may determine when. Where may be determined by
both pathways.
Electrical stimulation of the CDt revealed that the CDt possesses a mechanism to guide saccade initiation. That the CDt
actually uses the mechanism to guide saccades was suggested by
our next observation that CDt neurons increased their activity
before saccades to objects (Fig. 12). When there is only a single
object, we may make a saccade to it regardless of what the object
is. But when there are multiple objects, what information becomes critical because we need to choose one of them before
making a saccade. Indeed, in such a multiple-object condition,
CDt neurons often became active before saccades if they were
directed to the preferred object of the neuron and if the object was
present in the preferred location of the neuron (Fig. 12C). This
finding suggests that individual CDt neurons control the initiation of saccades that are directed to particular objects.
The CDt is part of the basal ganglia, which are highly developed in the primate. There, we found highly object-selective and
position-selective visual signals. Unexpected for such high visual
sensitivity, the CDt has a remarkable motor function: its activation can induce saccadic eye movements. To our knowledge, this
type of motor functionality has never been demonstrated in an
area with sharp object selectivity. Therefore, the CDt may be
uniquely situated to guide gaze accurately to selected visual objects in complex visual environments. When and how the CDt
uses the mechanism to select visual objects will be addressed in
future studies.
References
Beckstead RM, Edwards SB, Frankfurter A (1981) A comparison of the intranigral distribution of nigrotectal neurons labeled with horseradish peroxidase in the monkey, cat, and rat. J Neurosci 1:121–125.
Boussaoud D, Desimone R, Ungerleider LG (1991) Visual topography of
area TEO in the macaque. J Comp Neurol 306:554 –575.
Brown VJ, Desimone R, Mishkin M (1995) Responses of cells in the tail of
the caudate nucleus during visual discrimination learning. J Neurophysiol 74:1083–1094.
Bruce CJ, Goldberg ME, Bushnell MC, Stanton GB (1985) Primate frontal
eye fields. II. Physiological and anatomical correlates of electrically
evoked eye movements. J Neurophysiol 54:714 –734.
Caan W, Perrett DI, Rolls ET (1984) Responses of striatal neurons in the
behaving monkey. 2. Visual processing in the caudal neostriatum. Brain
Res 290:53– 65.
DiCarlo JJ, Maunsell JH (2003) Anterior inferotemporal neurons of monkeys engaged in object recognition can be highly sensitive to object retinal
position. J Neurophysiol 89:3264 –3278.
Goodale MA, Milner AD (1992) Separate visual pathways for perception
and action. Trends Neurosci 15:20 –25.
Hays AV Jr, Richmond BJ, Optican LM (1982) Unix-based multipleprocess system, for real-time data acquisition and control. WESCON
Conf Proc 1–10.
Hikosaka O, Wurtz RH (1983a) Visual and oculomotor functions of monkey substantia nigra pars reticulata. I. Relation of visual and auditory
responses to saccades. J Neurophysiol 49:1230 –1253.
Hikosaka O, Wurtz RH (1983b) Visual and oculomotor functions of monkey substantia nigra pars reticulata. IV. Relation of substantia nigra to
superior colliculus. J Neurophysiol 49:1285–1301.
Hikosaka O, Sakamoto M, Usui S (1989) Functional properties of monkey
caudate neurons. I. Activities related to saccadic eye movements. J Neurophysiol 61:780 –798.
Hikosaka O, Takikawa Y, Kawagoe R (2000) Role of the basal ganglia in the
control of purposive saccadic eye movements. Physiol Rev 80:953–978.
Janssen P, Srivastava S, Ombelet S, Orban GA (2008) Coding of shape and
position in macaque lateral intraparietal area. J Neurosci 28:6679 – 6690.
11016 • J. Neurosci., August 8, 2012 • 32(32):11005–11016
Karabelas AB, Moschovakis AK (1985) Nigral inhibitory termination on efferent neurons of the superior colliculus: an intracellular horseradish peroxidase study in the cat. J Comp Neurol 239:309 –329.
Kitama T, Ohno T, Tanaka M, Tsubokawa H, Yoshida K (1991) Stimulation
of the caudate nucleus induces contraversive saccadic eye movements as
well as head turning in the cat. Neurosci Res 12:287–292.
Lehky SR, Peng X, McAdams CJ, Sereno AB (2008) Spatial modulation of
primate inferotemporal responses by eye position. PLoS One 3:e3492.
Liu P, Basso MA (2008) Substantia nigra stimulation influences monkey
superior colliculus neuronal activity bilaterally. J Neurophysiol 100:
1098 –1112.
Malpeli JG, Baker FH (1975) The representation of the visual field in the
lateral geniculate nucleus of Macaca mulatta. J Comp Neurol 161:569 –
594.
Middleton FA, Strick PL (1996) The temporal lobe is a target of output from
the basal ganglia. Proc Natl Acad Sci U S A 93:8683– 8687.
Mishkin M, Ungerleider LG, Macko KA (1983) Object vision and spatial
vision: two cortical pathways. Trends Neurosci 6:414 – 417.
Miyashita Y, Higuchi S, Sakai K, Masui N (1991) Generation of fractal patterns for probing the visual memory. Neurosci Res 12:307–311.
Murata A, Gallese V, Luppino G, Kaseda M, Sakata H (2000) Selectivity for
the shape, size, and orientation of objects for grasping in neurons of
monkey parietal area AIP. J Neurophysiol 83:2580 –2601.
Op De Beeck H, Vogels R (2000) Spatial sensitivity of macaque inferior
temporal neurons. J Comp Neurol 426:505–518.
Parthasarathy HB, Schall JD, Graybiel AM (1992) Distributed but convergent ordering of corticostriatal projections: analysis of the frontal eye field
and the supplementary eye field in the macaque monkey. J Neurosci
12:4468 – 4488.
Peng X, Sereno ME, Silva AK, Lehky SR, Sereno AB (2008) Shape selectivity
in primate frontal eye field. J Neurophysiol 100:796 – 814.
Plenz D, Kitai ST (1998) Up and down states in striatal medium spiny neurons simultaneously recorded with spontaneous activity in fast-spiking
interneurons studied in cortex-striatum-substantia nigra organotypic
cultures. J Neurosci 18:266 –283.
Rainer G, Miller EK (2000) Effects of visual experience on the representation of objects in the prefrontal cortex. Neuron 27:179 –189.
Rainer G, Asaad WF, Miller EK (1998) Memory fields of neurons in the
primate prefrontal cortex. Proc Natl Acad Sci U S A 95:15008 –15013.
Rao SC, Rainer G, Miller EK (1997) Integration of what and where in the
primate prefrontal cortex. Science 276:821– 824.
Yamamoto et al. • What and Where Visual Information in Caudate Tail
Robinson DA (1972) Eye movements evoked by collicular stimulation in
the alert monkey. Vision Res 12:1795–1808.
Robinson DA, Fuchs AF (1969) Eye movements evoked by stimulation of
frontal eye fields. J Neurophysiol 32:637– 648.
Saint-Cyr JA, Ungerleider LG, Desimone R (1990) Organization of visual
cortical inputs to the striatum and subsequent outputs to the pallidonigral complex in the monkey. J Comp Neurol 298:129 –156.
Saleem KS, Logothetis NK (2007) A combined MRI and histology atlas of
the rhesus monkey brain. New York: Academic.
Selemon LD, Goldman-Rakic PS (1985) Longitudinal topography and interdigitation of corticostriatal projections in the rhesus monkey. J Neurosci 5:776 –794.
Sereno AB, Amador SC (2006) Attention and memory-related responses of
neurons in the lateral intraparietal area during spatial and shape-delayed
match-to-sample tasks. J Neurophysiol 95:1078 –1098.
Sereno AB, Lehky SR (2011) Population coding of visual space: comparison
of spatial representations in dorsal and ventral pathways. Front Comput
Neurosci 4:159.
Sereno AB, Maunsell JH (1998) Shape selectivity in primate lateral intraparietal cortex. Nature 395:500 –503.
Shibutani H, Sakata H, Hyvärinen J (1984) Saccade and blinking evoked by
microstimulation of the posterior parietal association cortex of the monkey. Exp Brain Res 55:1– 8.
Shook BL, Schlag-Rey M, Schlag J (1991) Primate supplementary eye field.
II. Comparative aspects of connections with the thalamus, corpus striatum, and related forebrain nuclei. J Comp Neurol 307:562–583.
Stanton GB, Goldberg ME, Bruce CJ (1988) Frontal eye field efferents in the
macaque monkey: I. Subcortical pathways and topography of striatal and
thalamic terminal fields. J Comp Neurol 271:473– 492.
Tanaka K (1996) Inferotemporal cortex and object vision. Annu Rev Neurosci 19:109 –139.
Van Hoesen GW, Yeterian EH, Lavizzo-Mourey R (1981) Widespread corticostriate projections from temporal cortex of the rhesus monkey.
J Comp Neurol 199:205–219.
Webster MJ, Bachevalier J, Ungerleider LG (1995) Transient subcortical
connections of inferior temporal areas TE and TEO in infant macaque
monkeys. J Comp Neurol 352:213–226.
Yeterian EH, Van Hoesen GW (1978) Cortico-striate projections in the rhesus monkey: the organization of certain cortico-caudate connections.
Brain Res 139:43– 63.